Iron deficiency alters dopamine transporter functioning in rat striatum
Iron deficiency alters dopamine transporter functioning in rat striatum
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DOI：
10.1093/jn/130.11.2831
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发表时间：
2000-11-01
影响因子：
4.2
通讯作者：
Beard, JL
中科院分区：
文献类型：
--
作者：
Erikson, KM;Jones, BC;Beard, JL
生命早期缺铁性贫血在体内和体外评价多巴胺（DA）功能方面产生了深刻的变化。本研究采用行为学和生物化学方法来研究铁缺乏大鼠纹状体DA代谢改变的生物学基础。目的是确定是否DA转运蛋白（DAT）功能改变断奶后缺铁。雄性和雌性21日龄的Sprague-Dawley大鼠（n = 40）喂养铁缺乏（ID）的饮食（3毫克铁/公斤的饮食）或对照（CN）饮食（35毫克铁/公斤的饮食）4周前的行为测试。对分级剂量的运动活动反应（3.75 - 30 mg/kg体重）的DA摄取抑制剂可卡因在缺铁大鼠中显著减弱，雄性和雌性的半数最大有效剂量（ED 50）均增加50（氯化萘-雌性，7.1 +/-0.9毫克/千克; ID-雌性，11.2 +/-1.3毫克/千克;氯化萘-雄性，12.0 +/-0.7毫克/千克; ID-雄性，17.0 +/-1.8毫克/千克）。用H-3 - 1-（2-（二苯基甲氧基）-乙基）-4-（3-苯基丙基）哌嗪（H-3-GBR 12935）进行的放射性配体结合试验表明，缺铁不会改变配体对DAT的亲和力，但会显著降低尾壳核中转运蛋白的密度，降低30%，尾壳核中转运蛋白的密度降低20%。铁缺乏也显着降低H-3-DA摄取到纹状体突触体，但不影响释放的DA与氯化钾刺激。这些实验提供了支持的证据表明，铁缺乏大鼠纹状体细胞外DA水平升高可能是DAT功能降低而不是释放速率增加的结果。
Iron deficiency anemia in early life produces profound changes in both in vivo and in vitro evaluations of dopamine (DA) functioning. This study employed both behavioral and biochemical approaches to examine the biological bases of alterations in striatal DA metabolism seen in iron-deficient rats. The purpose was to determine whether the DA transporter (DAT) was functionally altered in postweaning iron deficiency. Male and female 21-d-old Sprague-Dawley rats (n = 40) were fed either an iron-deficient (ID) diet (3 mg Fe/kg diet) or a control (CN) diet (35 mg Fe/kg diet) for 4 wk before behavioral testing. Motor activity responses to graded doses (3.75-30 mg/kg body) of the DA uptake inhibitor, cocaine, were significantly blunted in iron-deficient rats with a 50% higher half-maximal effective dose (ED50) in both males and females (CN-female, 7.1 +/- 0.9 mg/kg; ID-female, 11.2 +/- 1.3 mg/kg; CN-male, 12.0 +/- 0.7 mg/kg; and ID-male, 17.0 +/- 1.8 mg/kg). Radioligand binding assays with H-3-1-(2- (diphenylmethoxy)-ethyl)-4-(3-phenylpropyl) piperazine (H-3-GBR12935) demonstrated that iron deficiency did not alter the affinity of the ligand for the DAT but did significantly decrease the density of the transporter by 30% in caudate putamen and 20% in nucleus accumbens. Iron deficiency also significantly decreased H-3-DA uptake into striatal synaptosomes, but did not affect release of DA with potassium chloride stimulation. These experiments provide supporting evidence that elevated levels of extracellular DA in the striatum of iron-deficient rats is likely to be the result of decreased DAT functioning and not increased rates of release.